Extended Data Fig. 6: Increased physical activity and improvement in metabolic health markers in OVX VMHvlMC4R::hM3Dq female mice in response to acute and chronic CNO.
From: Oestrogen engages brain MC4R signalling to drive physical activity in female mice
a, Distance travelled over time in OVX female VMHvlCre− (n = 5) and VMHvlMC4R::hM3Dq (n = 5) mice during administration of plain H2O or CNO-H2O (repeated-measures two-way ANOVA interaction effect F11,88 = 5.265, P < 0.0001). b, Total dark period rearing events in intact and OVX female mice administered plain H2O or CNO-H2O drinking water (repeated-measures two-way ANOVA interaction effect F1,8 = 60.31, P < 0.0001 post hoc P < 0.0001). c, Body weights (repeated-measures two-way ANOVA time effect F2,24 = 49.51, P < 0.0001; genotype effect F2,24 = 33.50, P < 0.0001) and fasting glucose levels (repeated-measures two-way ANOVA time effect F2,26 = 6.456, P = 0.0053; genotype effect F1,26 = 10.11, P = 0.0038) in female mice after OVX and subsequent HFD feeding. d, Blood glucose (left) and AUC (right) during ITT in chow-fed OVX female mice following 6-hour fast and saline/CNO treatment. e, Blood glucose (left, repeated-measures two-way ANOVA interaction effect F1,8 = 7.791, P = 0.0235, post hoc: VMHvlMC4R::hM3Dq saline versus CNO, T15 P = 0.0009 and T60 P = 0.0318) and AUC (right, repeated-measures ANOVA with mixed-effects model, note: one cre+ female with missed injection was included in saline but not CNO treated groups, interaction effect F1,8 = 7.791, P = 0.0235, post hoc: VMHvlMC4R::hM3Dq saline versus CNO P = 0.0007) values during 90 min ITT test on HFD-fed OVX female mice performed 6 hours post fasting and post injection with saline or CNO. f, Blood glucose levels following a 6 h fast in OVX female mice maintained on Chow/HFD following a single saline or CNO injection (repeated-measures ANOVA with mixed-effects model, note: one cre+ female with missed injection was included in saline but not CNO treated groups, Chow: treatment effect F1,17 = 5.038, P = 0.0384, post hoc P = 0.0179; and HFD: interaction effect F1,17 = 20.47, P = 0.0019, post hoc P = 0.0073). g, Percentage change in body weight in HFD-fed OVX female mice (n = 5/5) continuously administered CNO-laden drinking water (repeated-measures two-way ANOVA interaction effect F7,64 = 4.583, P = 0.0003. h, Fasting blood glucose levels in OVX/HFD mice before and after 8 days of chronic CNO (repeated-measures ANOVA with mixed-effects model, note: one cre+ female with missed injection was included in saline but not CNO treated groups, interaction effect F1,17 = 5.180, P = 0.0361 post hoc: VMHvlMC4R::hM3Dq Pre versus Post P = 0.0156). i, Plasma cholesterol levels before (Pre) and after (Post) 8 days of continuous CNO-H2O exposure (repeated-measures ANOVA with mixed-effects model, note: one cre+ female with missed injection was included in saline- but not CNO-treated groups, interaction effect F1,8 = 5.502, P = 0.0470, post hoc P = 0.0203). j, Average daily food intake during 8 days of continuous CNO-H2O exposure (points represent separate daily measurements of average consumption per mouse). Data are mean ± s.e.m. or box plots (described in Fig. 1c legend). a–h, ANOVA with Holm–Šidák multiple comparisons test.
